CDX-1 and CDX-2 are expressed in human colonic mucosa and are down-regulated in patients with Hirschsprung's disease associated enterocolitis

Abstract

Caudal type homeobox gene-1 and -2 (CDX-1 and CDX-2), homologues of the Drosophila homeobox gene caudal, encode transcription factors in endoderm derived tissues of the intestine. CDX genes control proliferation and differentiation of intestinal mucosal cells and colon cancer cells. Hirschsprung's Disease (HD) or congenital intestinal aganglionosis, a major developmental anomaly of intestine, which causes functional intestinal obstruction, is frequently associated with enterocolitis. Aetiology of HD-associated enterocolitis (HDEC) remains obscure. Reduction of gut mucosal enteroendocrine cells, and inefficient transfer of the secretory immunoglobulin A across the gut mucosal cell were shown to be associated with enterocolitis in HD patients suggesting that mucosa may directly involve in the pathophysiology of HDEC. This study aims to ascertain whether the CDX-1 and CDX-2 genes, that control the proliferation and differentiation of mucosal cells, play a role in HDEC. Using semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) and in situ hybridisation, we analysed the expression of CDX-1 and CDX-2 genes in colon specimens of normal controls, necrotising enterocolitis (NEC) infants, and HD patients with and without enterocolitis. We showed for the first time that CDX-1 and CDX-2 genes were expressed in the colonic mucosal epithelium in normal, NEC and in HD infants. However, the expressions of both genes were reduced in patients with HDEC. Our findings suggest that reduced expression of CDX-1 and CDX-2 genes in mucosa may be associated with the development of HDEC. © 2001 Elsevier Science B.V. All rights reserved.